Multilayer medical devices

ABSTRACT

A medical device includes at least four layers including a first material and a second material having a different stiffness than a stiffness of the first material, wherein at least one of the layers varies in thickness axially along the device.

RELATED APPLICATION

This patent application is related to U.S. patent application Ser. No.______ [Attorney Docket No. 10527-443001], entitled “Medical Balloons”,filed concurrently herewith and incorporated by reference in itsentirety.

TECHNICAL FIELD

The invention relates to multilayer medical devices, such as, forexample, medical tubing, guide wires, and catheters.

BACKGROUND

Intravascular medical devices such as, for example, guide wires,catheters, and medical tubing, allow physicians to perform a medicalprocedure, such as angioplasty or delivery of an endoprosthesis. In somecases, a device is inserted into a patient's vascular system at aconvenient site and subsequently delivered, e.g., pushed, through thevascular system to a target site. The path that the device takes throughthe vascular system to the target site can be relatively tortuous, forexample, requiring the device to change direction frequently.

In some circumstances, it is desirable for the device to have relativelygood trackability so that it can travel along the tortuous path. At thesame time, the device preferably has good pushability so that forcesapplied proximally to the device can be transmitted distally to deliverthe device.

SUMMARY

The invention relates to multilayer medical devices, such as, forexample, medical tubing, guide wires, and catheters.

In one aspect, the invention features a medical device having variableor differential stiffness along a length, e.g., the axial length, of thedevice. For example, a medical device may include a first portion, e.g.,a proximal portion, that is relatively stiffer that a second portion,e.g., a portion distal of the first portion. As a result, in someembodiments, the device can have good trackability, e.g., at therelatively more flexible distal portion, and/or good pushability, e.g.,at the relatively stiffer proximal portion.

In another aspect, the invention features a medical device including atleast four layers including a first material and a second materialhaving a different stiffness than a stiffness of the first material,wherein at least one of the layers varies in thickness axially along thedevice.

Embodiments may include one or more of the following features. Thedevice is stiffer at a proximal end than at a distal end. The deviceincludes at least five layers, e.g., at least seven layers or at least13 layers. The device has the same number of layers for substantiallythe entire length of the device.

Various embodiments of layers are possible. The layers can extendsubstantially the length of the device. At least one of the layers canvary in thickness for substantially the entire length of the device. Atleast one of the layers can vary in thickness at a selected portion ofthe device. At least one of the layers can vary in thickness at morethan the one selected portions of the device. The layers of differentmaterials can vary in thickness at different selected portions of thedevice and/or at about the same selected portion of the device.

Various embodiments of materials are possible. The first and secondmaterials can alternate. The first and second materials can includeblock copolymers including common block moieties, such as amide segmentsand tetramethylene glycol segments. The first and/or second material canbe selected from a group consisting of thermoplastic polyamides,thermoplastic polyesters, and thermoplastic elastomers. The first and/orsecond material can be a blend of polymers.

The device can be an extruded device. The device can be in the form of atube, a catheter shaft, or a guide wire.

In another aspect, the invention features a medical device including afirst layer formed of a first material, a second layer formed of asecond material having a different stiffness than a stiffness of thefirst material, and a third layer comprising an adhesive materialbetween the first and second layers, wherein the first layer varies inthickness along an axial portion of the device.

In another aspect, the invention features a method of making a medicaldevice. The method includes forming a tube including at least threelayers formed of a first material and a second material having adifferent stiffness than a stiffness of the first material, and varyingthe thickness of at least one of the layers axially along the device.The method can include co-extruding the layers. The method can includeforming the tube into a guide wire.

Embodiments may have one or more of the following advantages. Themedical devices can have one or more relatively gradual transitionsbetween portions having different stiffness, materials, and/or hardness.As a result, the devices can be less susceptible to kinking or buckling,which can occur in devices having abrupt changes, e.g., in stiffness,materials, and/or hardness. The physical properties, e.g., stiffness, ofthe devices, can be customized. The medical devices can be moreresistant to damage.

Other aspects, features and advantages of the invention will be apparentfrom the description of the preferred embodiments and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is an illustration of a multilayer tube.

FIG. 2 is a cross sectional view of a wall of the tube of FIG. 1, takenalong line 2-2.

FIG. 3 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 4 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 5 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 6 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 7 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 8 is a cross sectional view of an embodiment of a wall of medicaldevice.

FIG. 9 is an assembly drawing of an extrusion crosshead.

FIG. 9 a is a cross-sectional view of the first crosshead disc in FIG. 9according to one embodiment.

FIG. 9 b is a cross-sectional view of the second crosshead disc in FIG.9 according to one embodiment.

FIG. 9 c is a cross-sectional view of the third, fifth, seventh, ninth,and eleventh crosshead discs in FIG. 3 according to one embodiment.

FIG. 9 d is a cross-sectional view of the fourth, sixth, eighth, tenthand twelfth crosshead discs in FIG. 3 according to one embodiment.

FIG. 9 e is a cross-sectional view of the thirteenth crosshead disc inFIG. 9 according to one embodiment.

FIG. 9 f is a cross-sectional view of assembly sections 226 and 228according to one embodiment.

FIG. 9 g is a cross-sectional view of assembly section 224 according toone embodiment.

FIG. 9 h is a cross-sectional view of assembly section 222 according toone embodiment.

FIG. 9 i is a cross-sectional view of a mandrel according to oneembodiment.

FIG. 9 j is a cross-sectional view of assembly section 230 according toone embodiment.

FIG. 9 k is a cross-sectional view of the nozzle according to oneembodiment.

FIG. 10 is an assembly drawing of a crosshead arrangement according toan embodiment.

FIG. 11 a is a cross-sectional view of the first crosshead disc in FIG.9 according to one embodiment.

FIG. 11 b is a cross-sectional view of the second crosshead disc in FIG.9 according to one embodiment.

FIG. 11 c is a cross-sectional view of the third, fifth, seventh, ninth,and eleventh crosshead discs in FIG. 3 according to one embodiment.

FIG. 11 d is a cross-sectional view of the fourth, sixth, eighth, tenthand twelfth crosshead discs in FIG. 3 according to one embodiment.

FIG. 11 e is a cross-sectional view of the thirteenth crosshead disc inFIG. 9 according to one embodiment.

FIG. 12 is a cross sectional view of an embodiment of a wall of medicaldevice.

DETAILED DESCRIPTION

Referring to FIGS. 1 and 2, a tube 10 having variable or differentialstiffness along its length (longitudinal or axial axis A) is shown. Tube10 includes a wall 12 of constant thickness formed of multiple layers,in this example, nine, thin layers, 14, 16, 18, 20, 22, 24, 26, 28, and30. Layers 14, 18, 22, 26, and 30 are formed of a first material, andalternate with layers 16, 20, 24, and 28, which are formed of a secondmaterial different than the first material, e.g., having differentcomposition, strength, hardness, and/or stiffness. As shown, layers 14,16, 18, 20, 22, 24, 26, 28, and 30 vary in thickness along axis A oftube 10. Layers 16, 20, 24, and 28 have a thickness T₁, at a proximalportion 32 of tube 10, decrease distally in thickness at a selectedtransition portion 34 of the tube, and have a thickness T₂, which isless than T₁, at a distal portion 36. Conversely, layers 14, 18, 22, 26,and 30 are generally thicker at distal portion 36 than at proximalportion 34, and vary in thickness at portion 34. By controlling thethickness of one or more layers of tube 10, the stiffness of the tubealong axis A can be controlled.

For example, layers 14, 18, 22, 26, and 30 can be formed of the firstmaterial, such as PEBAX® 7033 (69 Shore D, available from Atofina,Philadelphia, Pa.) and layers 16, 20, 24, and 28 can be formed of astiff (relative to the first material) second material, such as PEBAX®7233 (72 Shore D). By distally decreasing the thickness of layers 16,20, 24, and 28, the amount of stiff material at distal portion 36 alsodecreases relative to the amount of stiff material at proximal portion34. As a result, since there is less stiff material at distal portion36, i.e., more flexible material, the distal portion is more flexiblethan proximal portion 32. Thus, when tube 10 is formed, for example,into a guide wire or a catheter (e.g., a balloon catheter), relativelystiff proximal portion 32 can provide the tube with good pushability,while relatively flexible distal portion 36 can provide the tube withgood trackability to navigate through tortuous paths.

Without wishing to be bound by theory, it is believed that the multitudeof layers provides tube 10 with a relatively gradual transition betweendifferent portions or layers of materials, and differing physicalproperties, e.g., stiffness. It is believed that an abrupt transitioncan cause a tube to be more susceptible to unpredictable kinking orbuckling, which can occur during use and is typically undesirable. Byusing a multitude of layers, the materials are distributed evenly toapproximate homogenous blending or mixing of the materials, e.g., as ina solid solution, so that there is a reduced possibility of a localizedconcentration of a material that can disproportionately contribute totube 10.

The stiffness of a portion of tube 10 can be controlled by controllingdesign parameters such as, among others, the materials used in thelayers and their amounts (e.g., concentrations), the placement of thematerials in a radial direction of the tube, and/or the number of layersthe tube includes, which is related to the placement of the materials.Generally, stiffer materials tend to provide stiffer tubes or tubeportions. For substantially similar tubes, a tube having a higher amountor concentration of a stiff material tends to be stiffer than anothertube having a lower amount or concentration of the stiff material. Forexample, a first portion of a tube having a ratio of PEBAX® 7233 (72Shore D) to PEBAX® 7033 (69 Shore D) of 3:1 is typically stiffer than asecond tube portion having a PEBAX® 7233:PEBAX® 7033 ratio of 2:1because the first portion has more stiff material (PEBAX® 7233) than thesecond portion.

The placement of the materials in a radial direction of the tube alsoaffects the stiffness of the tube or tube portion. In some embodiments,forming one or more layers of a stiff material radially farther or awayfrom axis A typically increases the stiffness of the tube. For example,a two-layer tube having flexible material as an inner layer (closer toaxis A) and stiff material as an outer layer tends to be stiffer than atwo-layer tube in which the flexible material is formed as the outerlayer and the stiff material is formed as the inner layer. It isbelieved that the farther away a layer is from axis A, the more effectthe layer can have on the moment of inertia of a tube. For example, astiff layer radially farther away from axis A can enhance the stiffnessof a tube more than when the stiff layer is radially closer to axis A.

Related to the placement of materials is the number of layers that atube includes. For example, assuming the tube wall thickness remainsconstant, a two-layer tube portion having flexible material as the innerlayer and stiff material as the outer layer tends to be more stiff thana four-layer tube portion having alternating layers of flexible materialand stiff material, in which the innermost layer is formed with flexiblematerial. In the two-layer portion, all the soft material is in onelayer and is close to axis A. In comparison, in the four-layer portion,some of the stiff material has been formed radially closer to axis A. Asdescribed above, forming a stiff material radially farther from axis Aenhances the stiffness of the tube. Thus, in this example, increasingthe number of layers and forming the stiffer material closer to axis A(or forming more flexible material farther away from axis A) decreasesthe stiffness of the tube. This example assumes that the ratio of stiffto flexible materials remain the same, but generally, the stiffness of aportion of the tube is dependent on multiple (e.g., all) of the designparameters. The effects of the concentrations of materials, the numberof layers, and their radial placement on the stiffness of a tube arepresented in Example 1 below.

The number of layers is generally two or more. For example, the numberof layers can be at least two, at least three, at least four, at leastfive, at least six, at least seven, at least eight, at least nine, atleast 10, at least 11, at least 12, at least 13, at least 14, at least15, at least 16, at least 17, at least 18, at least 19, at least 20, ormore. In certain embodiments, the number of layers is less than 100(e.g., less than 90, less than 80, less than 70, less than 60, less than50, less than 40, less than 35, less than 30, less than 25, less than20, less than 15, or less than 10). The number of layers may be, forexample, seven, thirteen, twenty or more.

One or more of the layers varies in thickness along the length of tube10. As shown in FIG. 2, the layers, e.g., layers 16, 20, 24, and 28, canhave a first constant thickness, e.g., at proximal portion 32 and asecond constant thickness different than the first thickness, e.g., lessthan the first thickness at distal portion 36. Between portions 32 and36, as shown, at transition portion 34, the thickness of the layerschanges in thickness. Similarly, layers 14, 18, 22, 26, and 30 aregenerally thicker at distal portion 36 than at proximal portion 34, andvary in thickness at transition portion 34. One or more of the layerscan have more than two different portions having different thickness.

In other embodiments, a tube includes more than one transition portions34, e.g., two, three, four, five, more than five, more than ten, etc.Referring to FIG. 3, a tube wall 40 includes seven layers, 42, 44, 46,48, 50, 52, and 54 formed of two different materials. Layers 44, 48, and52 vary in thickness from a first thickness T₃ at proximal portion 32,through a first transition portion 56, to an intermediate portion 57having a second thickness T₄, through a second transition portion 58,and to a third thickness T₅ at distal portion 36. As shown, T₄>T₃>T₅. Insome embodiments, if layers 44, 48, and 52 are formed of a materialstiffer than the material of layers 42, 46, 55, and 54, thenintermediate portion 57 is the stiffest portion, followed by the portionproximal of the intermediate portion, and followed by the portion distalof the intermediate portion. In some embodiments, one or more of layers42-54 can be made of different materials. Transition portions 56 and 58can be located at different axial positions, as described below (FIG.8). Within a layer, the composition can change, for example, layer 44can change from a soft material to a stiff material to soft material.

In certain embodiments, the layers vary in thickness along the entirelength of a tube. Referring to FIG. 4, a tube wall 60 includes fivelayers 62, 64, 66, 68, and 70 formed of two different materials. Layers64 and 68 decrease in thickness from proximal portion 32 to distalportion 36. If layers 64 and 68 are formed of a material stiffer thanthe material of layers 62, 66, and 70, then distal portion 36 tends tobe less stiff than proximal portion 32. If layers 64 and 68 are formedof a material more flexible than the material of layers 62, 66, and 70,then distal portion 36 tends to be stiffer than proximal portion 32. Inother embodiments, the layers vary in thickness along less than theentire length of tube 10, e.g., less than 90%, 80%, 70%, 60%, 50%, 40%,30%, or 20%, as determined from either end of the tube.

The layers can be asymmetrically distributed in the radial direction ofthe tube. For example, referring to FIG. 5, a tube wall 80 includes fivelayers 82, 84, 86, 88, and 90 formed of two materials. Layers 84 and 88are arranged closer to an outer surface of tube wall 80 than to an innersurface. In other embodiments, the layers can be evenly distributedalong in the radial direction of the tube (e.g., as shown in FIG. 2).

Tube 10 can be formed of two or more different materials, e.g., three,four, five, ten, or more. FIG. 6 shows a tube wall 92 having elevenlayers 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, and 114 formed ofthree materials. Layers 94, 98, 102, 106, 110, and 114 are formed of afirst material; layers 96, 104, and 112 are formed of a second material;and layers 100 and 108 are formed of a third material. As shown, all thelayers vary in thickness similarly to the embodiment shown in FIG. 2,e.g., having transition portions 34 generally at the same axialposition. In other embodiments, a tube may include multiple transitionportions located at different axial positions. Referring to FIG. 8, atube 140 includes eleven layers 142, 144, 146, 148, 150, 152, 154, 156,158, 160, and 162 formed of three materials. Layers 148 and 156 have atransition portion 164 that is more proximal than transition portion 166of layers 144, 152, and 160. In some embodiments, layers 148 and 156 canbe made of the same material as layers 144, 152, and 160. Thisconfiguration may enhance the transition to provide a relatively smoothtransition.

Alternatively or in addition, one or more of the layers can terminatewithin the tube wall. Referring to FIG. 7, a tube wall 116 formed ofthree different materials includes two layers 124 and 130 that terminatealong the length of the tube wall. As a result, at proximal portion 32,tube wall 16 includes eleven layers formed of layers 118, 120, 122, 124,126, 128, 130, 132, and 134; and at distal portion 36, the tube wallincludes seven layers formed of layers 118, 120, 122, 126, 128, 132, and134.

A tube can have any combination of the layers described above, formed oftwo or more materials. For example, a tube can have one or more layersof layer 16, layer 44, and/or layer 64, arranged evenly apart orasymmetrically (e.g., as shown in FIG. 5). One or more layers of layer16, layer 44, and/or layer 64 can have one or more transition portions(e.g., as shown in FIGS. 6 and 8). The number of layers can change alongthe axial direction of the tube.

In certain embodiments, one or more layers can have along their axiallengths a minimum thickness of at least about 0.02 micron (e.g., atleast about 0.05 micron, at least about 0.1 micron, at least about 0.25micron, at least about 0.5 micron, at least about 0.75 micron, at leastabout one micron, at least about 1.5 microns, at least about 2 microns,at least about 2.5 microns, at least about 3 microns, at least about 3.5microns), and/or a maximum thickness of at most about 20 microns (e.g.,at most about 15 microns, at most about 10 microns, at most about ninemicrons, at most about eight microns, at most about seven microns, atmost about six microns, at most about five microns, at most about fourmicrons, at most about three microns, at most about two microns, at mostabout one micron, at most about 0.5 micron, at most about 0.25 micron).The thicknesses of the layers are dependent on, e.g., the thickness ofthe device being formed, the number of layers, the materials of thelayers, and/or the configurations of the layers.

Along a portion of a tube, the thickness of the flexible and stifflayers may be different or the same. In some relatively stiff portions,the flexible layers make up from about one percent to about 45% (e.g.,from about 5% to about 45%, from about 5% to about 40%), about 30% orless, from about 20% to about 30%) of the total tube wall thickness andstiff polymer makes up the balance. In certain relatively flexibleportions, the stiff layers make up from about one percent to about 45%(e.g., from about 5% to about 45%, from about 5% to about 40%, about 30%or less, from about 20% to about 30%) of the total tube wall thicknessand flexible polymer makes up the balance. As a result, for a devicewith a comparable number of flexible and stiff layers, the flexiblepolymer layers may be thinner or thicker than the stiff polymer layers.The thickness of the layers may vary progressively in a radialdirection. For example, the layers may get thicker from the outermostlayer to the innermost layer or vice versa. The thickness of the layersof one type (flexible or stiff) may vary while the layers of the othertype are constant.

In some embodiments, layers may be formed of stiff or hard polymer thathas a hardness of more than about 60 Shore D, preferably 65 Shore D ormore, and softer polymer that has a hardness of about 60 Shore D orless. In some embodiments, the flexible or soft polymer can have ahardness of greater than about 60 Shore D, but it is still softer thanthe hard polymer. The difference in hardnesses of adjacent bonded layerscan be about 40 Shore D or less, preferably 20 Shore D or less, whichcan enhance compatibility between the layers, reduce delamination at theinterface, and/or increase ease of coextruding. Hardness may be measuredaccording to ASTM D2240. The layers can alternate between hard and softpolymer. The layers may be of progressively increasing hardness. Forexample, the layers may be of progressively increasing hardness from theoutermost layer to the innermost layer. For example, for a support usedfor stent delivery, the outermost layer can be a soft layer that absorbsand distributes stress and abrasion imposed by the stent.

The layers may be of substantially pure polymer or they may be blends ofdifferent polymers. All of the soft (or hard) layers may be made of thesame soft (or hard) polymer or the different soft (or hard) layers maybe made of different polymers. The soft and hard can be made of blockcopolymers including common block moieties, which can enhancecompatibility, while maintaining defect retardation. For example, theblock moieties may be amide segments and tetramethylene glycol segments.

An example is the PEBAX® family of polymers, which can be used pure oras blends (available from Atofina, Philadelphia, Pa.). For example,PEBAX® 5533 (55 Shore D) can be blended with PEBAX® 2533 (25 Shore D) ina weight ratio of about 4 to 1 to provide a soft polymer of about 50Shore D. Another combination of hard and soft polymers is polybutyleneterephthalate (PBT) such as CELANEX® (over 80 Shore D, from Ticona,Summit, N.J.) and polyester/ether block copolymer available as ARNITEL®(55 Shore D, from DSM, Erionspilla, Ind.). A combination of hard andsoft polymers is PBT and one or more PBT thermoplastic elastomers, suchas RITEFLEX® (55 Shore D from Ticona in Summit, N.J.) and HYTREL® (55Shore D from E. I. Dupont de Nemours, Wilmington, Del.) for example.Still another combination of hard and soft polymers is polyethyleneterephthalate (PET) and a thermoplastic elastomer, such as a PBTthermoplastic elastomer (e.g., ARNITEL®, HYTREL®, or RITEFLEX®).

In certain embodiments, one or more layers can contain one or morenylons. For example, one or more of the hard polymer layers can containone or more nylons. For example, a combination of hard and soft polymersis a nylon and a PEBAX®-type material, such as PEBAX®, GRILON®,GRILAMID® (EMS) and/or VESTAMID® (Creanova).

Examples of nylons include aliphatic nylons, such as Nylon 11 (ElfAtochem), Nylon 6 (Allied Signal), Nylon 6/10 (BASF), Nylon 6/12 (AshleyPolymers) and Nylon 12.

Additional examples of nylons include aromatic nylons, such as GRIVORY®(EMS) and Nylon MXD-6. Other nylons and/or combinations of nylons can beused.

In some embodiments, one or more layers can contain a liquid crystalpolymer (LCP) (e.g., a composite material having the LCP incorporatedtherein). Examples of LCPs include polyester(s), polyamide(s) and/ortheir copolymers, such as VECTRA® A (Ticona), VECTRA® B (Ticona) andVECTRA® LKX (Ticona) (e.g., VECTRA® LKX 1111 (Ticona)). Other LCPsand/or combinations of LCPs can be used.

The LCP can be incorporated into one or more polymers, such as, forexample, a PEBAX®-type material, a nylon, a thermoplastic polyesterand/or thermoplastic elastomer versions thereof. In certain embodiments,the liquid crystal polymer can be incorporated into one or more of thepolymer layers to form a hard layer of material (e.g., a layer ofmaterial with more than about 60 Shore D hardness, such as more thanabout 65 Shore D hardness).

In a preferred combination, an LCP is incorporated into a layercontaining one or more PEBAX®-type materials, such as PEBAX®, GRILON®,GRILAMID®, and/or VESTAMID®. In certain embodiments, an LCP-containingcomposition can be relatively stiff in the direction of melt flow.Without wishing to be bound by theory, it is believed that this mayresult because LCP crystals (e.g., fibers) form or align in the meltflow direction as the polymer composite cools from a liquid state to asolid state.

The amount of LCP contained in the tube can vary depending upon itsintended use. In some embodiments, as the percentage of LCP in acomposite material is decreased, the individual layer thickness and theoverall thickness of one or more layers of an LCP-containing compositematerial, e.g., in a tube, can be increased.

The LCP content of a tube can be at least about 0.1 weight percent, suchas from about 0.1 weight percent to about 20 weight percent (e.g., fromabout 0.5 weight percent to about 10 weight percent, from about one toabout five weight percent). Within a given layer, the LCP content can beat least about 0.1 weight percent (e.g., from about one weight percentto about 50 weight percent, from about five weight percent to about 20weight percent, from about five weight percent to about 15 weightpercent).

The percentage of layers containing LCP relative to the total number oflayers can be from about one percent to about 80 percent (e.g., at leastabout five percent, at least about 10 percent, at least about 15percent, at least about 20 percent, at least about 25 percent, at leastabout 30 percent, at least about 35 percent, at least about 40 percent,at most about 80 percent, at most about 75 percent, at most about 70percent, at most about 65 percent, at most about 60 percent, at mostabout 55 percent, at most about 50 percent, at most about 45 percent).

In certain embodiments, an adhesion enhancing material can beincorporated into one or more material layers. An adhesion enhancingmaterial can be used, for example, to enhance the adhesion betweenadjacent layers. Examples of adhesion enhancing materials include epoxyor anhydride modified polyolefins, such as LOTADER® (Elf Atochem) andKODAR® PETG (Eastman Kodak). An adhesion enhancing material can be addedto a material (e.g., a composition containing one or more polymers)prior to extrusion (described below). For example, in embodiments inwhich alternate layers are formed of PET and PBT, PETG can be added tothe PET before extrusion.

The amount of adhesion enhancing material can vary depending upon theintended use. In some embodiments, a sufficient amount of adhesionenhancing material(s) are included in the material so that the adhesionenhancing material(s) makes up at least about 0.5 percent of theresulting mixture that forms the layer (e.g., at least about onepercent, at least about five percent, at least about 10 percent) and/orat most about 20 percent of the resulting mixture that forms the layer(e.g., at most about 15 percent, at most about 12 percent, at most about10 percent).

In certain embodiments, the adhesion between one or more adjacent layerscan vary as layer thickness is varied. Generally, embodiments canprovide adhesion between one or more (e.g., all) layers in a medicaldevice (e.g., a tube). For example, one or more (e.g., all) layers in amedical device (e.g., a tube) can demonstrate good adhesion when flexed,deflated and/or inflated. In some embodiments, a medical device (e.g., atube) can show good flexibility and/or adhesion (e.g., when one or morelayers are relatively thin).

In some embodiments, a compatibilizing material can be incorporated intoone or more material layers. The compatibilizing material can bedesigned, for example, to modify one or more phase boundaries of theLCP(s) and one or more of the other polymer(s) (e.g., thermoplasticpolymer(s)) and/or to enhance adhesion between the LCPs and one or moreof the other polymer(s). The compatibilizing material can be acopolymer, such as a block copolymer, including moieties of at least twodifferent chemical structures, respectively providing compatibility withan LCP and one or more other polymers in the mixture. Thecompatibilizing material can be a reactive polymer that reacts with theLCP and/or one or more other polymers in the mixture. Thecompatibilizing material can be a catalyst that promotes a reactionbetween the LCP and one or more other polymers in the mixture. Othercompatibilizing materials can be used. Combinations of compatibilizingmaterials can be used.

Examples of compatibilizing materials include copolyester elastomers,ethylene unsaturated ester copolymers, such as ethylene-maleic anhydridecopolymers, copolymers of ethylene and a carboxylic acid or acidderivative, such as ethylene-methyl acrylate copolymers, polyolefins orethylene-unsaturated ester copolymers grafted with functional monomers,such as ethylene-methyl acrylate copolymers, copolymers of ethylene anda carboxylic acid or acid derivative, such as ethylene-methyl acrylatemaleic anhydride terpolymers, terpolymers of ethylene, unsaturated esterand a carboxylic acid or acid derivative, such as ethylene-methylacrylate-methacrylic acid terpolymers, maleic acid graftedstyrene-ethylene-butadiene-styrene block copolymers, and acrylic acidelastomers, such as acrylic rubbers. Similar polymers containing epoxyfunctional groups, for instance derived from glycidyl methylacrylate(e.g., alkyl(meth)acrylate-ethylene-glycidyl (meth)acrylate polymers)can be used. Ionomeric copolymers can be used. PETG can be used.Examples of compatibilizing materials include HYTREL® HTR-6108,POLYBOND® 3009 (BP Chemicals), SP2205 (Chevron), DS1328/60 (Chevron),LOTADER® 2400, ESCOR® ATX-320, ESCOR® ATX-325, VAMAC® G1 and LOTADER®AX8660. In certain embodiments, a compatibilizing material (e.g., PETG)can be mixed with one or more polymers (e.g., an LCP-containingmaterial) prior to extrusion.

There are many ways in which LCPs can be blended into thermoplastics.The LCP blend can be a ternary system of LCP, thermoplastic andcompatibilizing materials. Systems with multiple combinations ofdifferent LCPs, different thermoplastics and different compatibilizingmaterials are contemplated.

The compatibilized blend can be a blend of polyazomethine LCP, athermoplastic polymer such as a polyamide, and a compatibilizingmaterial such as a caprolactum having at least one functional groupcapable of showing compatibility and/or reactivity to the LCP and/or thethermoplastic polymer. Such blends are described, for example, in U.S.Pat. No. 5,565,530, which is hereby incorporated by reference.

One polymer blend product which can be used include PET, a whollyaromatic LCP copolyester and an ethylene-methyl acrylate-acrylic acidterpolymer compatibilizing material, such as, for example, ESCOR®ATX320, ESCOR® ATX325, or ESCOR® XV-11.04. Another polymer blend productincludes PET, a wholly aromatic LCP copolyester and an ethylene-maleicanhydride copolymer compatibilizing material, such as POLYBOND® 3009.Another polymer blend product includes PET, a wholly aromatic LCPcopolyester and an ethylene-methyl acrylate copolymer grated with maleicanhydride compatibilizing material, such as DS 1328/60, or a copolyesterelastomer, such as HYTREL® HTR 6108.

Polymer blend products including PET, LCP and at least twocompatibilizing materials can be used. For example, DS 1328/60 andPOLYBOND® 3009 can be used with the LCP VECTRA®. As an additionalexample, when the LCP is VECTRA®, the compatibilizing materials can bePOLYBOND® 3009 and at least one additional compatibilizing materialselected from ESCOR® ATX-320, ESCOR® ATX-325, DS 1328160, ESCOR®XV-11.04 and HYTREL® HTR-6108.

In certain embodiments, consideration is given to the properties of theLCP and the other polymer(s) (e.g., PET), as well as the desiredproperties of the resulting blend, when selecting the compatibilizingmaterial(s).

In some embodiments containing an LCP, a thermoplastic polymer andcompatibilizing material(s), the blend product includes from about 0.1weight percent to about 10 weight percent (e.g., from about 0.5 weightpercent to about 2 percent) LCP, from about 40 weight percent to about99 weight percent (e.g., from about 85 weight percent to about 99 weightpercent) thermoplastic polymer, and from about 0.1 weight percent toabout 30 weight percent (e.g., from about one weight percent to about 10weight percent) compatibilizing material(s).

While certain polymers and polymer combinations are discussed above,other polymers and polymer combinations can also be used. Other polymersinclude, for example, elastomers such as thermoplastic elastomers andengineering thermoplastic elastomers, such as polybutyleneterephthalate-polyethene glycol block copolymers, which are available,for example, as HYTREL®. These are discussed in Hamilton U.S. Pat. No.5,797,877, the entire content of which is incorporated herein byreference. Other polymers include polyurethenes. Other polymers includecopolymers such as ABS (acrylonitrile-butadiene-styrene), ABS/nylon,ABS/-polyvinyl chloride (PVC), ABS/polycarbonate, acrylonitrilecopolymer, polyacrylamide, polyacrylate and polyacrylsulfone, polyesterssuch as polyethylene terephthalate (PET), polybutylene terephthalate(PBT), polyethylene naphthalate (PEN), liquid crystal polymer (LCP),polyester/polycaprolactone and polyester/polyadipate; and high melttemperature polyethers including polyetheretherketone (PEEK),polyethersulfone (PES), polyetherimide (PEI) and polyetherketone (PEK),polymenthylpentene, polyphenylene ether, polyphenylene sulfide, andstyrene acrylonitrile (SAN), polyamides such as nylon 6, nylon 6/6,nylon 6/66, nylon 6/9, nylon 6/10, nylon 6/12, nylon 1, nylon 12,ethylene, propylene ethylene vinylacetate and ethylene vinyl alcohol(EVA), various ionomers, polyethylene type I-IV, polyolefins,polyurethane, polyvinyl chloride, and polysiloxanes (silicones). Thosewith low to medium melt temperatures include fluorocarbons such aspolychlorotriethylene (CTFE), poly[ethylene-co-chlorotrifluoroethylene](ECTFE) copolymer ethylene tetrafluoroethylene (ETFE), copolymertetrafluoroethylene and hexafluoropropylene (FEP), perfluoroalkane (PFA)and poly[vinylidene fluoride] (PVDF).

The tubes can be prepared by an extrusion process. Generally, thisprocess can involve the use of an extrusion apparatus (e.g., acrosshead, such as a compact crosshead) having a series of discs. Forexample, the apparatus can have one disc per material layer. Each disccan have one or more channels (e.g., one channel, two channels, threechannels, four channels, five channels, six channels, seven channels,eight channels, 10 channels, 12 channels, 14 channels, 16 channels,etc.). In some embodiments, it can be desirable to have a relativelylarge number of channels (e.g., five, six, seven, eight, etc. channels)in at least one disc (e.g., in one disc, two discs, three discs, fourdiscs, five discs, six discs, seven discs, eight discs, etc.) to enhancethe degree of circularity of the layers. In some embodiments, each dischas a relatively large number of channels. The number of channels can beselected based upon, for example, the volumetric output, thetemperature, the viscosity, the pressure drop, the outer diameter of thediscs, the material (e.g., polymer(s)) used, and/or the channeldimensions.

In certain embodiments, the thickness of one or more of the discs (e.g.,at least two discs, at least three discs, at least four discs, at leastfive discs, at least six discs, at least seven discs, at least eightdiscs, at least nine discs, at least 10 discs, at least 11 discs, atleast 12 discs, at least 13 discs, at least 20 discs, etc., each disc)can be less than about one inch (e.g., less than about 0.75 inch, lessthan about 0.5 inch, less than about 0.4 inch, less than about 0.3 inch,less than about 0.2 inch, less than about 0.15 inch, less than about 0.1inch, less than about 0.05 inch) in the direction parallel to the flowof material (polymer) through the apparatus (e.g., in the direction Lshown in FIG. 9).

In some embodiments, an apparatus has a 13 disc stack having a totalthickness of less than about 13 inches (e.g.,. less than about 12inches, less than about 11 inches, less than about 10 inches, less thanabout nine inches, less than about eight inches, less than about seveninches, less than about six inches, less than about 5.5 inches, lessthan about five inches, less than about 4.5 inches, less than about fourinches, less than about 3.5 inches, less than about three inches, lessthan about 2.5 inches, less than about two inches, less than about 1.9inches, less than about 1.8 inches) in the direction parallel to theflow of material (polymer) through the apparatus (e.g., in the directionL shown in FIG. 9).

In certain embodiments, an apparatus has a 20 disc stack having a totalthickness of less than about 20 inches (e.g., less than about 19 inches,less than about 18 inches, less than about 17 inches, less than about 16inches, less than about 15 inches, less than 14 six inches, less thanabout 13 inches, less than about 12 inches, less than about 10 inches,less than about 9.5 inches, less than about nine inches, less than about8.5 inches, less than about eight inches, less than about 7.5 inches,less than about seven inches, less than about 6.5 inches, less thanabout 6.4 inches, less than about 6.3 inches, less than about 6.2inches, less than about 6.1 inches, less than about six inches) in thedirection parallel to the flow of material (polymer) through theapparatus (e.g., in the direction L shown in FIG. 9).

FIG. 9 shows a cross-sectional view of an embodiment of an extrusionapparatus (a compact crosshead) 220 that can be used in the preparationof a 13-layer tube. The tubes may be formed by co-extruding amulti-layer tube having the desired sequence of layers. Compactcrosshead 220 that includes a series of assembly sections 222, 224, 226,228, 230 with a common bore into which is placed a spacing mandrel 232that encompasses an air supply tube 234. Assembly sections 222, 224, 226define inlets 236, 238 from separate extruders (not shown) which feeddifferent polymers (in this example polymer A and polymer B) into thehead and include passageways 240, 242 which direct the polymers toassembly section 228.

Assembly section 228 houses a series 244, in this example thirteen,extrusion discs. Each of the discs includes passageways for bothpolymers but an extrusion inlet and outlet for only one of the polymers.(An exception is the last disc which includes a passageway for only onepolymer.) In this way, the polymer flow continues along the assembly buteach polymer is added to the extrusion stream in the desired order. Inthis example, every other disc has an inlet and outlet for the firstpolymer and every other intervening disc has an inlet and outlet for thesecond polymer.

FIGS. 9 a-9 e show five different four channel disc designs that can beused together in crosshead 220. The inlets and outlets of the discs areformed as machined channels in the face of the discs. Polymer A flowsthrough a passageway 250 and polymer B flows through a passageway 251.(An opening 255 for an alignment pin is provided for registration of thediscs.) The outlets are formed by channels 256 that lead to gaps betweenadjacent discs. For example, the first disc 246 has an inlet 252 and anoutlet 247 for the first polymer and passageway 251 for the secondpolymer but no inlet or outlet for the second polymer. The second disc248 has an inlet 254 and an outlet 249 for the second polymer and apassageway 259 for the first polymer but no inlet or outlet for thefirst polymer. As a result, the first polymer will be deposited as theinnermost layer, the second polymer as the next adjacent layer, thefirst polymer will be the third layer and so on. At the end of thethirteenth disc a thirteen layer extrusion in which alternate layers ofdifferent polymers is achieved. The thirteenth disc (FIG. 9 e) is formedwithout passageway 51. The extrusion is sized to the desired diameter atthe nozzle 250 on assembly section 230. The crosshead provides forsubstantial flexibility in a compact design by changing the discs oroutlet configurations of the discs to obtain a desired sequence oflayers. As illustrated in the mechanical drawings, the diameter of thecentral opening in the discs can vary to facilitate polymer deliveryalong the stream. In addition, the channels can be arranged to directpolymer(s) into the stream at different radial orientations insuccessive discs.

The number of layers can be varied from a single layer, two layers,three layers or more layers by controlling the number of discs.Referring as well to FIG. 10, a twenty-disc arrangement, the system canas well be adapted for co-extruding a greater number of polymers byreplacing sections 224, 226, with sections that include additionalextruder inlets and configuring the discs to include channels toaccommodate the flow of the additional polymers. In the embodiment ofFIG. 9, the assembly sections and the discs are formed of stainlesssteel and the system has an overall diameter, D, of about 3.5 inch andan overall length, L, of about 6.5 inch. The extruders may be one-inchBrabrender extruders (N.J.). Some illustrative operating conditions,such as zone heating temperatures, polymer concentrations, feed rate,and line speed, are described in U.S. Ser. No. 09/798,749, entitled“Multilayer Medical Device” and filed on Mar. 2, 2001, herebyincorporated by reference in its entirety.

FIGS. 11 a through 11 e show five different eight channel disc designsthat can be used together in crosshead 220 in a manner similar to thatdescribed above with respect to the four channel discs shown in FIGS. 9a through 9 e. As shown in FIGS. 11 a through 11 e, however, these discseach have eight channels 256. This can result in the velocity of thepolymer flow at outlet 247 being more uniform around the perimeter ofoutlet 247, thereby promoting circularity of individual layers in atube, and/or increasing circularity of the interfaces between layers ina tube. The eight-channel pattern can be machined into the same sizediscs as the four-channel pattern so that the four and eight channeldiscs may be used with the same extrusion equipment. In certainembodiments, the width of the disc material between the channelsgenerally constrains their size and location on the discs. For example,in some embodiments, discs machined from 440C stainless steel maymaintain a minimum width between channels of about 0.035 inches withoutcracking under the pressure of the extruded polymer.

The thickness of individual layers can be controlled by controlling thefeed rate or flow of the polymer(s). For example, to increase thethickness of a layer, the flow of material to that layer is increased.To decrease the thickness the layer, the flow of material to that layeris decreased. The length of the transition portion(s) can be controlledby controlling the rate of change in the flow of the material. An abruptflow change tends to produce to a relatively short transition portion,and a relatively gradual change in flow can produce a relatively longtransition portion. Stopping the flow of material can cause a layer toterminate within the tube, e.g., layer 124 (FIG. 7). A preferred systemfor controlling the feed rate or flow of polymers, including melt pumps,and systems and methods for controlling the pumps, is described in WO01/32398, entitled “Method and Apparatus for Extruding Catheter Tubing”,hereby incorporated by reference in its entirety. Other methods includeusing servo-controlled valves, as described in Burlis et al., U.S. Pat.No. 3,752,617, hereby incorporated by reference.

OTHER EMBODIMENTS

In other embodiments, a tube wall may include an adhesive layer betweenlayers of other materials. Referring to FIG. 12, a tube wall 300includes nine layers 302, 304, 306, 308, 310, 312, 314, 316, and 318.Layers 302, 310, and 318 are formed of a first material; layers 306 and314 are formed of a second material; and layers 304, 308, 312, and 316are formed of an adhesive. The adhesive can be used, e.g., when thefirst and second materials are immiscible. As shown, layers 304, 308,312, and 316 substantially match layers 306 and 314, but in otherembodiments, layers 304, 308, 312, and 316 can be formed in anyconfiguration described above.

Layers 304, 308, 312, and 316 can be formed any adhesive materialappropriate for use in a medical device. The adhesive can be a polymer(e.g., a substantially pure polymer, or a blend of polymers). As anexample, in certain embodiments, the adhesive is formed of an ethylenevinyl acetate polymer-containing material. As another example, in someembodiments, the adhesive is formed of an anhydride-modified polyolefin.An adhesive can be selected, for example, from the BYNEL® family ofpolymers (e.g., BYNEL® CXA Series, BYNEL® 1000 Series, BYNEL® 1123,BYNEL® 1124, BYNEL® 11E554, BYNEL® 11E573, BYNEL® CXA E-418),commercially available from E. I. DuPont de Nemours (Wilmington, Del.),the PLEXAR® family of polymers (e.g., PX360, PX360E, PX380, PX3227,PX3236, PX3277, PX5125, PX5327, PX206, PX209, PX2049, PX165, PX175,PXI80, PX909, PX101, PX107A, PX108, PXI 14, PX1164), commerciallyavailable from Equistar Chemicals (Newark, N.J.), and/or the BLOX®family of polymers (e.g., BLOX® 200 Series), commercially available fromthe Dow Chemical Company (Midland, Mich.).

As an example, layers 302, 310, and 318 can be formed of anypolyester-containing material (e.g., a substantially pure polyester, ablend containing at least one polyester) appropriate for use in amedical device. Such polymers include, for example, polyesterhomopolymers and/or copolymers (e.g., block copolymers) of polyesters.Examples of polyesters include PET polymers, PBT polymers and blends andcombinations thereof, such as the SELAR® PT family of polymers (e.g.,SELAR® PT 8307, SELAR® PT4274, SELAR® PTX280, DuPont (Wilmington,Del.)), the CLEARTUF® family of polymers (e.g., CLEARTUF® 8006, M&GPolymers (Apple Grove, W. Va.)), the TRAYTUF® family of polymers (e.g.,TRAYTUF® 1006, Shell Chemical (Houston, Tex.), the MELINAR® family ofpolymers, DuPont, the CELANEX® family of polymers, Ticona (Summit,N.J.), the RITEFLEX® family of polymers, Ticona, the HYTREL® family ofpolymers (e.g., HYTREL® 5556, HYTREL® 7246, HYTREL® 4056), DuPont, andthe ARNITEL® family of polymers (e.g., ARNITEL® EM630), DSM(Erionspilla, Ind.).

Layers 306 and 314 can be formed of any polyamide-containing material(e.g., a substantially pure polyamide, a blend containing at least onepolyamide) appropriate for use in a medical device. Such polymersinclude, for example, polyamide homopolymers and/or copolymers (e.g.,block copolymers) of polyamides. One type of polyamide includes thenylon family of polymers, including, for example, aliphatic nylons andaromatic nylons, such as, e.g., Nylon 11 (Atofina (Philadelphia, Pa.)),Nylon 6 (Honeywell (Morristown, N.J.)), Nylon 6/10 (BASF (Mount Olive,N.J.)), Nylon 6/12 (Ashley Polymers (Cranford, N.J.)), Nylon 12, NylonMXD-6, the GRIVORY® family of polymers (EMS (Sumter, S.C.)), theGRILAMID® family of polymers (EMS), the VESTAMID® family of polymers(Daicel-Degussa Ltd), and the PEBAX® family of polymers (e.g., PEBAX®5533, PEBAX® 2533, PEBAX® 7033, Atofina).

The tubes described above can be formed into a guide wire, e.g., apolymer guide wire. Methods of making a guide wire, including one havinggood torque transmission is described in U.S. Pat. No. 5,951,494, herebyincorporated by reference in its entirety.

Example 1

The following example shows the results from simulations studying theeffect of the number of layers and their radial placement on thestiffness of a tube. The layers in the samples discussed belowalternate. The wall thickness remained constant for all samples. Thecalculations are based on uniformly distributed layers of equalthickness. TABLE 1 Sample Material (Wt. Percent) Layer Stiffness(g-mm/deg) A PEBAX ® 7033 Single 0.545 B PEBAX ® 7033/7233 (50/50)2-layer, 7033 outer 0.664 C PEBAX ® 7033/7233 (35/65) 2-layer, 7033outer 0.711 D PEBAX ® 7033/7233 (35/65) 7-layer, 7033 outer 0.723 EPEBAX ® 7033/7233 (35/65) 13-layer, 7033 outer 0.737 F PEBAX ® 7233/7033(65/35) 13-layer, 7233 outer 0.739 G PEBAX ® 7233/7033 (50/50) 2-layer,7233 outer 0.752 H PEBAX ® 7233/7033 (65/35) 7-layer, 7233 outer 0.761 IPEBAX ® 7233/7033 (65/35) 2-layer, 7233 outer 0.796 J PEBAX ® 7233Single 0.867

Sample A is a tube formed of pure PEBAX® 7033, and Sample J is a tubeformed of pure PEBAX® 7233, which is stiffer than PEBAX® 7033, asindicated by the higher stiffness (0.867 vs. 0.545 g-mm/deg).

Sample B is a two-layer tube, in which the outer layer is PEBAX® 7033and the inner layer is PEBAX® 7233. The ratio of PEBAX® 7033 to PEBAX®7233 is 50:50. The stiffness of Sample B is higher than the stiffness ofSample A because, compared to Sample A, there is more stiff material,i.e., PEBAX® 7233 (a stiff material) has replaced PEBAX® 7033 (a moreflexible material). Compared to Sample J, Sample B is less stiff becausethe stiff PEBAX® 7233 has been replaced by the more flexible PEBAX®7033.

Sample C is a two-layer tube, in which the outer layer is PEBAX® 7033and the inner layer is PEBAX® 7233. The ratio of PEBAX® 7033 to PEBAX®7233 is 35:65. Compared to Sample B, Sample C is more stiff becauseSample C has more stiff material—65% PEBAX® 7233 vs. 50% PEBAX® 7233.

Sample D is a seven-layer tube, in which the outer layer is PEBAX® 7033,and the ratio of PEBAX® 7033 to PEBAX® 7233 is 35:65. Compared to SampleC, Sample D is stiffer because more of the PEBAX® 7233 has beendistributed to the outer surface of the tube. That is, whereas in SampleC, all of the PEBAX® 7233 was adjacent to the inner surface of the tube,in Sample D, some of the PEBAX® 7233 has been moved radially outward,thereby affecting the moment of inertia of the tube more.

Sample E is a thirteen-layer tube, in which the outer layer is PEBAX®7033, and the ratio of PEBAX® 7033 to PEBAX® 7233 is 35:65. Compared toSample D, Sample E is stiffer because more of the PEBAX® 7233 has beendistributed to the outer surface of the tube.

Sample F is a thirteen-layer tube, in which the outer layer is PEBAX®7233, the ratio PEBAX® 7233 to PEBAX® 7033 is 65:35. Compared to SampleE, Sample F is stiffer because the stiff material (PEBAX® 7233) isformed on the outer surface of the tube. The difference is lesspronounced than when the stiff and flexible materials change positionsin Samples C and I because of the larger number of layers.

Sample G is a two-layer tube in which the outer layer is PEBAX® 7233,the ratio PEBAX® 7233 to PEBAX® 7033 is 50:50. Compared to Sample B,Sample G is stiffer because the stiffer PEBAX® 7233 is formed on theouter surface of the tube.

Sample H is seven-layer tube in which the outer layer is PEBAX® 7233,the ratio PEBAX® 7233 to PEBAX® 7033 is 65:35. Compared to Sample F,Sample H is stiffer because more of the PEBAX® 7233 has been distributedto the outer surface of the tube. Compared to Sample D, Sample H isstiffer because the stiffer PEBAX® 7233 is formed on the outer surfaceof the tube.

Sample I is a two-layer tube in which the outer layer is PEBAX® 7233,the ratio PEBAX® 7233 to PEBAX® 7033 is 65:35. Compared to Sample C,Sample I is stiffer because the stiffer PEBAX® 7233 is formed on theouter surface of the tube. Compared to Samples F and H, Sample I isstiffer because more of the PEBAX® 7233 has been distributed, e.g.,concentrated to the outer surface of the tube. However, compared toSample J, Sample I is less stiff because some of the PEBAX® 7233 hasbeen replaced by the more flexible PEBAX® 7033.

EXAMPLE 2

A nine-layer tube (0.022″ O.D.×0.017″ I.D.) having alternating layers ofPEBAX 7233 and PEBAX 5533 (i.e., a ABABABABA construction where PEBAX5533 was the “A” layer and PEBAX 7233 was the “B” layer) was made by thefollowing procedures.

Two extruders (Brabender Prepcenters (Type D-5 1)) were used, each with¾″ barrels (05-09-N55). One extruder fed PEBAX 7233 and the otherextruded PEBAX 5533. The temperatures (in Fahrenheit) were80-345-365-385 for both extruders. For the PEBAX 7233, the temperaturesforward of the clamp were 395-395-395, and for the PEBAX 5533, thetemperatures forward of the clamp were 385-385-395.

Two pumps (Zenith, 0.16 cc/rev) were used. For the PEBAX 7233 pump, theefficiency was 83.6%, and for the PEBAX 5533, the efficiency was 88.3%.The efficiencies affect the pump settings to get a given amount ofmaterial. The inlet pressure for the pumps was about 1500 psi.

The extrusion head was the same as that described in U.S. Ser. No.09/798,749, with eight-channel disks. A LaserMike192 was used gauge theO.D., and a Nikon toolscope with Quadrachek200 was used to visuallyexamine the tubes. A puller (Model Tapertube 0.5, having an OLCservo-controlled air box, from RDN Manufacturing Co., Inc.,Bloomingdale, Ill.) was used, and a water bath was set at 70° F.

The extrusion was based on distance down a part. That is, gearpumpchanges were based on movement of the tube, not, for example, based ontime. For example, once two inches of tube has been extruded, the firstmelt/gear pump would go from no movement to 7.84 rpm. After 504 incheshas been extruded, the same pump would go back to zero rpm. The cyclerepeats itself. Distance Melt pump 1 Melt pump 2 AirVoltage (in.) (rpm)(rpm) (IV = about 3 inches H₂O) 0 0 7.42 4.95 0.5 0 0 4.95 2 7.84 0 4.95378 7.84 0 4.5 380 7.84 0 5 504 7.84 0 5 504.5 0 0 5 505 0 7.42 5 649 07.42 5.8 919 0 7.42 5.45 920 0 7.42 5.1 999 0 7.42 4.95

A linear interpolation was used between consecutive points. The tube wasabout 83 feet long. In a 50-inch length, a transition was achieved fromabout 8% PEBAX 7233, mainly in the inner layers, to about 55% PEBAX7233, mainly in the outer layers. Thee system took approximately twohours to achieve equilibrium so that the relative amounts of eachmaterial were substantially constant along the length of the piece.

All of the features disclosed herein may be combined in any combination.Each feature disclosed may be replaced by an alternative feature servingthe same, equivalent, or similar purpose. Thus, unless expressly statedotherwise, each feature disclosed is only an example of a generic seriesof equivalent or similar features.

All publications, applications, and patents referred to in thisapplication are herein incorporated by reference to the same extent asif each individual publication or patent was specifically andindividually indicated to be incorporated by reference in theirentirety.

Other embodiments are within the claims.

1. A medical device, comprising: at least four layers comprising a firstmaterial and a second material having a different stiffness than astiffness of the first material, wherein at least one of the layersvaries in thickness axially along the device.
 2. The device of claim 1,wherein the device is stiffer at a proximal end than at a distal end. 3.The device of claim 1, wherein the first and second materials alternate.4. The device of claim 1, wherein the layers extend substantially thelength of the device.
 5. The device of claim 1, comprising at least fivelayers.
 6. The device of claim 1, comprising at least seven layers. 7.The device of claim 1, comprising at least 13 layers.
 8. The device ofclaim 1, wherein the device has the same number of layers forsubstantially the entire length of the device.
 9. The device of claim 1,wherein the at least one of the layers varies in thickness forsubstantially the entire length of the device.
 10. The device of claim1, wherein the at least one of the layers varies in thickness at aselected portion of the device.
 11. The device of claim 1, wherein theat least one of the layers varies in thickness at more than the oneselected portions of the device.
 12. The device of claim 1, whereinlayers of different materials vary in thickness at different selectedportions of the device.
 13. The device of claim 1, wherein layers ofdifferent materials vary in thickness at about the same selected portionof the device.
 14. The device of claim 1, wherein the first and secondmaterials comprise block copolymers including common block moieties. 15.The device of claim 14, wherein the block moieties are amide segmentsand tetramethylene glycol segments.
 16. The device of claim 1, whereinthe first and/or second material is selected from a group consisting ofthermoplastic polyamides, thermoplastic polyesters, and thermoplasticelastomers.
 17. The device of claim 1, wherein the first and/or secondmaterial is a blend of polymers.
 18. The device of claim 1, in the formof a tube.
 19. The device of claim 1, in the form of a catheter shaft.20. The device of claim 1, in the form of guide wire.
 21. The device ofclaim 1, wherein the device is an extruded device.
 22. A medical device,comprising: a first layer formed of a first material; a second layerformed of a second material having a different stiffness than astiffness of the first material; and a third layer comprising anadhesive material between the first and second layers, wherein the firstlayer varies in thickness along an axial portion of the device.
 23. Amethod of making a medical device, comprising: forming a tube comprisingat least three layers formed of a first material and a second materialhaving a different stiffness than a stiffness of the first material; andvarying the thickness of at least one of the layers axially along thedevice.
 24. The method of claim 23, comprising co-extruding the layers.25. The method of claim 23, further comprising forming the tube into aguide wire.